In recent years there have been provided devices or bandages for delivery of drugs to and through the skin or mucosa of the wearer as a means of providing continuous, controlled administration to the circulation thereby avoiding the uncertainties of oral administration and the inconvenience of administration by injection. Some of the best known applications of such transdermal administrations are the administration of nitroglycerine and of scopolamine.
Much patent literature has appeared directed to various devices for transdermal administration. Most of these are directed to various systems or structures and materials for improved delivery. Many of these systems have been developed as a method for delivering steroidal drugs and some of the devices employing such systems have been adapted for application with other drugs. When it is attempted to employ these developed systems with other drugs, problems have been encountered which have demonstrated that known systems are not necessarily applicable to all types of drugs.
Generally, the structure of a transdermal bandage or device consists of (a) a transdermal delivery system comprising an impermeable backing, a drug-containing reservoir, a rate-controlling membrane on the side to be ultimately proximate to the skin of the patient and (b) a means of attaching the system to the dermal surface. In the known systems, the reservoir, the source of supply for the drug, whether a single solid unit, a walled unit or a unit employing drug containing micro-capsules within the reservoir structure, contains the drug partly in particulate form and partly in solution i.e., contains drug in excess of its saturation solubility. During use, the drug in solution migrates to the permeable membrane surface, passes through the membrane and onto the skin for absorption. As the dissolved drug passes through the membrane some of the undissolved drug dissolves and there is, until the supply of undissolved drug is exhausted, a mixture of both dissolved and undissolved drug in the reservoir. The presence of dissolved and undissolved drug is considered necessary to provide for the near zero order rate of delivery, zero order being the rate of delivery which is constant or independent of time. It has been found, however, that when certain drugs such as, for example, timolol, are employed in a unitary solid reservoir of dissolved and undissolved drug, the dissolved drug often slowly crystallizes subsequent to fabrication. When crystallization occurs especially when accompanied by the formation of large crystals, dissolution, rather than diffusion, becomes the rate limiting process in drug release, thereby impairing the predictability of release rate and consequently the desired control in the administration of the drug. Such bandages would not be suitable for use in controlled therapy. Even if crystal size may be small enough to render the bandage utilizable, the waiting period necessary to complete the crystal formation can result in undesirable delay in manufacture. Moreover, at least in some cases, crystallization of a less preferred crystalline structure or separation of an amorphous form may occur which also may impair rate control. Thus, it is evident that for a transdermal bandage of certain drugs, the reservoir system containing both solid and dissolved drug has practical limitations in providing a less predictable delivery system.